8XJM

Latanoprost acid bound Prostaglandin F2-alpha receptor-Gq Protein Complex

8XJM の概要

• エントリーDOI: 10.2210/pdb8xjm/pdb
• EMDBエントリー: 38401
• 分子名称: Engineered miniGq, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• 機能のキーワード: cryo-em, complex, signaling protein, membrane protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 169208.66

構造登録者

Zhang, X.,Li, X.,Liu, G.,Gong, W. (登録日: 2023-12-21, 公開日: 2024-02-28, 最終更新日: 2024-10-23)

主引用文献

Li, X.,Zhang, X.,Wen, X.,Zhang, D.,Qu, C.,Miao, X.,Zhang, W.,Zhang, R.,Liu, G.,Xiao, P.,Sun, J.P.,Gong, W.
Structural basis for ligand recognition and activation of the prostanoid receptors.
Cell Rep, 43:113893-113893, 2024

PubMed Abstract: Prostaglandin F (PGF) and thromboxane A (TXA) are endogenous arachidonic acid metabolites, modulating diverse physiological processes including inflammation and cardiovascular homeostasis through activating PGF receptor (FP) and TXA receptor (TP). Ligands targeting FP and TP have demonstrated efficacy in treating conditions like glaucoma and cardiovascular diseases in humans, as well as reproductive-related diseases in animals. Here, we present five cryoelectron microscopy structures illustrating FP and TP in complex with G and bound to PGF (endogenous ligand), latanoprost acid (a clinical drug), and two other synthetic agonists. Combined with mutational and functional studies, these structures reveal not only structural features for the specific recognition of endogenous ligands and attainment of receptor selectivity of FP and TP but also the common mechanisms of receptor activation and G protein coupling. The findings may enrich our knowledge of ligand recognition and signal transduction of the prostanoid receptor family and facilitate rational ligand design toward these two receptors.

PubMed: 38446662
DOI: 10.1016/j.celrep.2024.113893

実験手法

ELECTRON MICROSCOPY (2.85 Å)